The long-term objectives of this project are to better understand the contribution of irregular vestibular nerve afferent fibers to the human vestibulo-ocular reflex (VOR), and to understand the functional impact of gentamicin's preferential toxicity on the region of the crista where irregular afferents predominate. During rapid head rotations, while viewing a near target, the VOR gain must increase to account for translation of the eyes with respect to the target. The neural substrate underlying these changes in VOR gain is unclear; however, the observation that this vergence-mediate gain increase is absent for ipsilesional head rotations in patients treated unilaterally with intratympanic gentamicin suggests that irregular vestibular nerve afferents may play a role in active modification of VOR gain (Migliaccio et al., 2004). Unlike regular vestibular afferents, irregular afferents are particularly sensitive to externally applied direct currents and their firing rate can be reduced by galvanic stimulation (Goldberg et al., 1984). Chen-Huang & McCrea (1998) showed in monkeys that when irregular afferents are galvanically inhibited, vergence-mediated modulation of the VOR is also reduced; however, the VOR gain during far viewing is unaffected by galvanic stimulation (Minor and Goldberg, 1991; Karlberg et al., 2000). The first goal of this project is to examine the effects of galvanic inhibition of irregular afferents on the human vergence-mediated VOR gain in normal subjects. If the vergence-mediated VOR gain is reduced during galvanic inhibition, then this would indicate that irregular afferents play an important role in increasing the VOR gain during near viewing. Our second goal is to repeat this experiment in patients treated with intratympanic gentamicin. If during rapid head rotations towards the gentamicin treated ear the vergence-mediated VOR is unaffected by galvanic inhibition, but is increased by galvanic excitation, then this would suggest that modulation of VOR gain by vergence depends upon irregular afferents that are preferentially affected by gentamicin and by galvanic stimuli. [unreadable] [unreadable]